3.2 FITB Practice

Types of White Blood Cells

• Neutrophils: 50-70%, numerous short-lived phagocytes
• Eosinophils: 1-5%, stain red, attack parasites
• Basophils: 0.1%, stain blue, release histamine
• Natural killer (NK) cells
• Mast cells

Phagocytosis

• Associated with Neutrophils, Monocytes, Macrophages
• Enzymes in lysosome digest bacterium, triggering an inflammatory response
• Phagocyte engulfs foreign particles or bacteria

Innate Immunity - Cell Mediated Immunity

• Cytotoxic or Killer Cells (CD8 T cells) are activated by the release of IL-2 from T helper cells
• CD8 cells recognize antigens on the surface of infected cells, attach to these cells, and secrete perforins
• Perforins punch holes into infected cells, killing them

Innate Immunity - TLRs

• Toll-Like Receptors (TLRs) are innate immune sensors
• TLRs trigger a cascade of events to kill or protect against pathogens
• They exist as transmembrane proteins, present on macrophages and a few other cells
• They are conserved across vertebrates, very important part of innate immune system
• They are sensitized to microbes (or their components)

Innate Immunity - Cytokines

• Cytokines are small proteins, secreted by cells of the immune system
• Examples include: Interferons, Interleukins, and Tumor Necrosis Factor (TNF)
• They affect the behavior of other cells, are signalling molecules, and key players in both innate and acquired immunity
• Cytokines are released by many cells of the immune system, including Neutrophils, Macrophages, Cytotoxic/Killer cells, and Lymphocytes

Innate Immunity - Interferon (IFN)

• Signalling proteins produced by virus-infected monocytes and lymphocytes
• Secreted proteins, key anti-viral proteins that inhibit protein synthesis
• Warn neighboring cells that a virus is around, triggering fever, cell death, and increased antibody production

Innate Immunity - Complement

• A large number of distinct plasma proteins that react with one another (C1-C9)
• Complement can bind to microbes and coat the microbes, facilitating phagocytosis and cause lysis of pathogens
• It is an essential part of innate immune response, enhancing the adaptive immune response

Innate Immunity - Inflammation

• A complex biological process by which the body responds to injury
• Macrophages release toxins (including reactive oxygen species or ROS) that injure tissues
• Chronic inflammation is almost always accompanied by tissue damage

Adaptive (Acquired) Immunity

• Immunity that develops after exposure, with the body remembering specific invader
• It relies heavily on the production of antibodies
• Passive or Active, Natural or Artificial

Humoral Immune Response

• An immune response involving direct contact (cells, molecules bind to receptors on cell surfaces) and cytokines
• Involves Antigen Presenting cells (APC), MHC, and the activation of B and T lymphocytes
• Release of cytokines stimulates cells to get activated, multiply, and release antibodies

CO2 Transport and Buffering

• CO2 is directly bound to Hemoglobin (at a site different from the one that binds Oxygen) in the blood.
• The rest of the CO2 is converted into Bi-Carbonate ions and Hydrogen ions (H+) by the Enzyme Carbonic Anhydrase.
• The reaction is reversible, proceeding to the right under conditions of lower temperature, higher pH, and increased oxygen pressure in the capillaries of the lungs.
• Only about 5% of the CO2 generated in the tissues dissolves directly in the plasma.

Bohr Effect and Haldane Effect

• The Bohr Effect: Hemoglobin releases oxygen in response to low pH, high temperature, and low oxygen pressure.
• The Haldane Effect: Hemoglobin releases CO2 in response to high pH, low temperature, and high oxygen pressure.

The Cardiovascular System and CO2

• CO2 is an acid, and its accumulation can lead to a drop in blood pH.
• The equation CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3− shows the conversion of CO2 into H+ and HCO3−.

Blood Clotting and Hemostasis

• Blood clotting has several positive feedback loops that amplify the clotting process.
• The TF-VII complex starts the clotting process, which activates Factor IX and X, leading to the formation of thrombin.
• Thrombin activates more Factors V, VIII, and XI, and also converts fibrinogen to fibrin.
• Platelets release thromboxane A2, which recruits and activates more platelets, and serotonin, which enhances their clumping and promotes blood vessel constriction.

Anticoagulants and Thrombocytopathics

• Direct-acting anticoagulants: Apixaban (Eliquis) and Rivaroxaban (Xarelto) are highly selective, orally bioavailable, and reversible direct inhibitors of factor X.
• Heparin: accelerates antithrombin III activity, which inactivates factors IX, X, and XI, and thrombin, preventing fibrin formation.
• Indirect-acting anticoagulants: Dicumarol or Warfarin sodium inhibits Vitamin K, which is necessary for the production of clotting factors II, VII, IX, and X.
• Platelet inhibitors (Thrombocytopathics): Aspirin inhibits thromboxane synthesis, resulting in decreased platelet aggregation, and dipyridamole causes vasodilation and increases blood flow, while inhibiting phosphodiesterase, resulting in reduced platelet aggregation.

Erythrocytes (RBCs)

• Males have approximately 5.4 million Erythrocytes per cubic millimeter of blood (range: 4.6 - 6.2 million), while females have about 4.8 million (range: 4.2 - 5.4 million).
• Males have approximately 10% more Erythrocytes than females.
• Normal Erythrocytes are biconcave disks about 7.5 micrometers in diameter with thicker edges than the center of the cell.
• The biconcave shape increases the surface area of the erythrocyte, making the movement of gases (oxygen and carbon dioxide) into and out of the cell more rapid.
• The erythrocyte can bend or fold around its thin center, decreasing its size and enabling it to pass more easily through small blood vessels.

RBC Factoids

• Women average about 4.8 million RBCs per cubic millimeter (mm3) of blood, while men average about 5.4 x 10^6 per µl.
• These values can vary depending on factors such as health and altitude.
• Peruvians living at 18,000 feet may have as many as 8.3 x 10^6 RBCs per µl.

RBC Development and Function

• RBC precursors mature in the bone marrow closely attached to a macrophage.
• They manufacture hemoglobin until it accounts for about 90% of the dry weight of the cell.
• The nucleus is squeezed out of the cell and is ingested by the macrophage.
• No longer needed proteins are expelled from the cell in vesicles called exosomes.
• RBCs are terminally differentiated, meaning they can never divide.
• They live about 120 days and then are ingested by phagocytic cells in the liver and spleen.
• Most of the iron in their hemoglobin is reclaimed for reuse.

Carbon Dioxide Transport

• About one-half of the CO2 is directly bound to hemoglobin (at a site different from the one that binds oxygen).
• The rest is converted into bicarbonate ions and hydrogen ions by the enzyme carbonic anhydrase.
• Bicarbonate ions diffuse back out into the plasma, while hydrogen ions bind to the protein portion of the hemoglobin.

Hemoglobin and Oxygen

• Under the conditions of lower temperature, higher pH, and increased oxygen pressure in the capillaries of the lungs, the reaction proceeds to the right, and deoxygenated hemoglobin becomes oxyhemoglobin.
• Under the conditions of higher temperature, lower pH, and lower oxygen pressure in the tissues, the reverse reaction is promoted, and oxyhemoglobin gives up its oxygen.

The Cardiovascular System

• The cardiovascular system distributes nutrients, oxygen, and hormones to all cells in the body and carries away metabolic waste products.
• The system consists of the heart, blood, arteries, arterioles, venules, and capillaries.

Blood

• Blood is composed of plasma and formed elements.
• Plasma makes up about 55% of the total blood volume and is composed of 92% water, electrolytes, and proteins.
• Formed elements include blood cells and platelets.
• Blood cells are divided into red blood cells (RBCs), which make up about 99.9% of all blood cells, and white blood cells (WBCs), which make up about 0.1% of all blood cells.
• RBCs have no nucleus and are biconcave in shape, with 95% of their composition made up of hemoglobin (Hb).
• Hb can reversibly bind 4O2 and 4CO2.

Platelets

• Platelets have no nucleus and are involved in blood clotting.
• They engulf and destroy pathogens, induce inflammation, and fight parasitic infections.
• Platelets produce antibodies and provide immunity.

Blood Clotting

• Hemostasis is the process of stopping bleeding, which involves platelet activation, clotting, and fibrinolysis.
• Platelets adhere to collagen in the damaged blood vessel wall, releasing thromboxane A2, which recruits and activates more platelets.
• The clotting process involves a series of coagulation factors, including thrombin, factor VII, and factor IX.
• Fibrinolysis is the process of breaking down the clot, which involves the conversion of plasminogen to plasmin by plasminogen activators.

Fibrinolysis

• Plasmin is generated from the enzymatic conversion of plasminogen.
• Plasmin lyses fibrin, degrades factors V and VIII, and inhibits further clotting.
• Plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase, convert plasminogen to plasmin.
• Antifibrinolytics, such as e-aminocaproic acid (EACA) and alpha2-antiplasmin, can be used to limit fibrinolytic activity.